Race and Outcomes of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

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Race and Outcomes of Autologous Hematopoietic CellTransplantation for Multiple Myeloma

PN Hari, MD, MS1, NS Majhail, MD, MS2,3, M-J Zhang, PhD1, A Hassebroek, MPH2, F Siddiqui,MD4, K Ballen, MD5, A Bashey, MD, PhD6, J Bird, MD7, CO Freytes, MD8, J Gibson, MD,PhD9, G Hale, MD10, L Holmberg, MD, PhD11, R Kamble, MD12, RA Kyle, MD13, HM Lazarus,MD14, CF LeMaistre, MD15, F Loberiza, MD, MS16, A Maiolino, MD, PhD17, PL McCarthy,MD18, G Milone, MD19, N Omondi20, DE Reece, MD21, M Seftel, MD22, M Trigg, MD23, DVesole, MD, PhD24, B Weiss, MD25, P Wiernik, MD26, SJ Lee, MD, MPH11, JD Rizzo, MD,MS1, and P Mehta, MD271 Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin,Milwaukee WI2 Center for International Blood and Marrow Transplant Research, National Marrow Donor Program,Minneapolis MN3 University of Minnesota, Minneapolis MN4 Medical College of Wisconsin5 Massachusetts General Hospital, Boston MA6 Blood and Marrow Transplant Group of Georgia, Atlanta GA7 Bristol Haematology And Oncology Centre, Bristol UK8 South Texas Veterans Health Care System and University of Texas Health Center at San Antonio,San Antonio TX9 Royal Prince Alfred Hospital, Camperdown, Australia10 A Children’s Hospital, Saint Petersburg FL11 Fred Hutchinson Cancer Research Center, Seattle WA12 Baylor College of Medicine, Houston TX13 Mayo Clinic, Rochester MN14 University Hospitals Case Medical Center, Cleveland OH15 Texas Transplant Institute, San Antonio TX16 University of Nebraska Medical Center, Omaha NE17 Hospital Univarstario Clementino Frago Filho, Rio de Janeiro Brazil18 Roswell Park Cancer Institute, Buffalo NY

Address for correspondence: Parameswaran Hari, MD, MS, CIBMTR, Medical College of Wisconsin, PO Box 26509, 8701 WatertownPlank Road, Milwaukee, WI 53226, Telephone: 414-805-4604, Fax: 414-805-4606, [email protected]'s Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customerswe are providing this early version of the manuscript. The manuscript will undergo copyediting typesetting and review of the resultingproof before it is published in its final citable form. Please note that during the production process errors may be discovered which couldaffect the content, and all legal disclaimers that apply to the journal pertain.

NIH Public AccessAuthor ManuscriptBiol Blood Marrow Transplant. Author manuscript; available in PMC 2011 March 1.

Published in final edited form as:Biol Blood Marrow Transplant. 2010 March ; 16(3): 395–402. doi:10.1016/j.bbmt.2009.11.007.

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19 Angelica Ocampo-Hospital and Research Center, Fundaleu Buenos Aires Argentina20 National Marrow Donor Program, Minneapolis MN21 University of Toronto, Toronto Ontario Canada22 CancerCare Manitoba, Manitoba Canada23 Merck & Co. Inc., Wilmington DE24 Loyola University Health System, Maywood IL25 Walter Reed Army Medical Center, Washington DC26 New York Medical College, Bronx NY27 University of Arkansas, Little Rock AR

AbstractBlacks are twice as likely to develop and die from multiple myeloma (MM) and are less likely toreceive an autologous hematopoietic-cell transplant (AHCT) for MM compared to whites. Theinfluence of race on outcomes of AHCT for MM is not well described. We compared the probabilityof overall survival, progression-free survival, disease progression and non-relapse mortality amongblack (N=303) and white (N=1892) recipients of AHCT for MM, who were reported to the Centerfor International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2005. The blackcohort was more likely to be female, had better Karnofsky performance scores but lower hemoglobinand albumin levels at diagnosis. Black recipients were younger and more likely to be transplantedlater in their disease course. Disease stage and treatment characteristics prior to AHCT were similarbetween the two groups. Black and white recipients had similar probabilities of 5-year overallsurvival (52% vs. 47%, P=0.19) and progression-free survival (19% vs. 21%, P=0.64) as well ascumulative incidences of disease progression (72% vs. 72%, P=0.97) and non-relapse mortality (9%vs. 8%, P=0.52). In multivariate analyses, race was not associated with any of these endpoints. Blackrecipients of AHCT for MM have similar outcomes compared to whites, suggesting that the reasonsunderlying lower rates of AHCT in blacks need to be studied further to ensure equal access to effectivetherapy.

KeywordsAutologous hematopoietic cell transplantation; multiple myeloma; race; survival; progression-freesurvival

BackgroundMultiple myeloma (MM) remains an incurable disease, although prognosis has improved inthe past decade.1,2 It is the most common hematologic malignancy among blacks and is theonly hematologic malignancy that is more frequent in this racial group compared with whites.In the United States, myeloma and its precursor disease monoclonal gammopathy ofundetermined significance (MGUS) are twice as common in blacks (annual incidence of14.4/100,000 in men and 9.8/100,000 in women compared with 6.6/100,000 in white men and4.1/100,000 in white women).1,3–7 Proposed factors to explain the increased incidence amongblacks include socioeconomic factors, greater exposure to hazardous materials, geneticpredisposition, greater degree of background antigenic stimulation, and a greater prevalenceof obesity.8–10 Mortality rates from MM in the United States are twice as high for blackscompared to whites (8.3/100,000 for men and 6.0/100,000 for women compared to 4.3/100,000and 2.8/100,000 for white men and women, respectively).11

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Socioeconomic factors that may impact access to cancer therapy and therapeutic choicesinclude place of residence, distance from care centers, unemployment, availability and qualityof health insurance, poor nutrition, exposure to infectious agents, lower educational level andannual income.12,13 Prior comparisons have drawn conflicting conclusions on treatmentoutcomes among blacks compared with white patients with MM. Savage et al found that blackpatients had shorter survival times following similar therapy for MM. Presentation at laterstages of disease, socioeconomic factors or differential access to care were thought to explainthis disparity.13,14 Other investigators have suggested that these disparities in outcomes areprimarily due to biological characteristics.15,16

Randomized clinical trials support the use of AHCT as a standard therapy for MM.17,18 Wehave previously shown that blacks are less likely to receive AHCT for MM compared withtheir age and sex matched white counterparts.19 In the current study, we compared outcomesbetween black and white patients receiving AHCT for MM to determine if disparate posttransplant outcomes validate lower AHCT use in blacks.

Patients and MethodsThe Center for International Blood and Marrow Transplant Research (CIBMTR) consists of avoluntary working group of more than 450 transplant centers worldwide. Centers contributedetailed data on consecutive allogeneic and autologous transplants to a statistical center ateither the Medical College of Wisconsin in Milwaukee or the National Marrow Donor ProgramCoordinating Center in Minneapolis. Subjects are followed longitudinally, with yearly follow-up. Computerized checks for errors, physicians’ review of submitted data and on-site audits ofparticipating centers ensure data quality. Observational studies conducted by the CIBMTR aredone with a waiver of informed consent and in compliance with HIPAA regulations asdetermined by the Institutional Review Board and the Privacy Officer of the Medical Collegeof Wisconsin.

PatientsThe study included 2195 (303 black and 1892 white) adult (age ≥ 18 years) recipients of AHCTfor MM who were transplanted between January 1995 and June 2005 (Table 1). Only recipientsof peripheral blood AHCT were included in this study; patients who had received plannedtandem AHCT (N=582) were excluded. Centers obtained information about patient race andthen reported it to the CIBMTR.

Statistical MethodsPatient-, disease- and treatment-related factors were compared between the black and whitecohorts, using Chi-square test for categorical and Kruskal-Wallis test for continuous variables.Outcomes analyzed included non-relapse mortality (NRM), relapse/progression, progression-free survival (PFS) and overall survival (OS). NRM was defined as death occurring in theabsence of relapse or progression of MM following AHCT. Responses, relapse/progressionwere defined according to standard criteria20. Chemotherapy sensitivity was defined asachievement of a partial or complete response to pretransplant therapy. PFS was defined assurvival without disease progression or relapse. Patients alive and with no evidence of diseaseprogression or relapse were censored at the time of last follow-up. The survival interval variablewas defined as time from the date of transplant to the date of death or last contact andsummarized by a survival curve. Probabilities of OS and PFS were calculated using the Kaplan-Meier estimator.21,22 NRM and relapse/progression were calculated using cumulativeincidence estimates. The log-rank test was used for univariate comparisons.

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Multivariate Cox proportional hazards regression was used to examine the outcomes betweenblack and white patient cohorts and to identify risk factors associated with outcomes.23 Astepwise forward selection multivariate model was built to identify covariates that influencedoutcomes. Any covariate with a P-value < 0.05 was considered significant. The proportionalityassumption for Cox regression was tested by adding a time-dependent covariate for each riskfactor and each outcome. Tests indicated that all variables met the proportional hazardsassumption. Results were expressed as relative risks (RR). Any risk factors found to besignificant were adjusted in the final Cox model. The main effect tested (i.e. black vs. white)was included in all models. The variables considered in multivariate analyses are summarizedin table 2. Analyses were performed using SAS software, version 9.1 (SAS Institute, Cary,NC).

ResultsPatient Characteristics

Table 1 shows the characteristics of all patients evaluated. Median ages at AHCT were 55 yearsfor black compared to 57 years for white patients (p<0.001). The black cohort had a higherproportion of females and patients with Karnofsky performance status scores (KPS) > 90 (69% vs. 61%, p=0.005). Blacks were more likely to have co-morbidities such as hypertension(47% vs. 25%, p<0.001), diabetes mellitus (17% vs. 9%, p<0.001), and obesity (38%vs. 31%,p=0.01). No statistically significant differences in disease stage or MM subtype were identified.Blacks were also more likely to have a lower hemoglobin (Hb <10 g/dL in 45% vs. 29%,p<0.001) at diagnosis. No significant differences in the levels of serum creatinine, beta-2microglobulin, calcium or marrow plasmacytosis were identified. The cohorts did not differwith respect to the type and number of prior therapies or sensitivity to therapies applied beforetransplantation. Blacks were transplanted later in the disease course, with 37% receiving AHCTa year or more from diagnosis vs. 28% in whites (p<0.001). There were no significantdifferences in conditioning regimens used or the receipt of a salvage second AHCT.

Non-relapse Mortality and Relapse/ProgressionFigure 1 shows the cumulative incidence of NRM. The cumulative incidence of NRM wassimilar in both groups. At 1 year was 5% (95% CI 4–6%) in whites vs. 3% (95% CI 2–6%) inblacks. At 5 years it was 8% (95% CI 7–9%) vs. 9% (95% CI 6–14%) in whites and blacksrespectively. In multivariate analysis (Table 3), race was not associated with NRM. Factorsassociated with an increased risk of NRM were age ≥ 65 years, KPS <90 and AHCT prior to2002.

Figure 2 shows cumulative incidence of relapse/progression. The cumulative incidence ofrelapse/progression was similar in both groups. At 1 year it was 27% (95% CI 25–29%) inwhites vs. 28% (95% CI 23–34%) in blacks. At 5 years it was 72% (95% CI 69–74%) vs. 72%(95% CI 65–78%) in whites and blacks respectively. In multivariate analysis (Table 3), racewas not associated with disease relapse or progression. Factors associated with an increasedrisk of relapse included KPS score < 90, Durie-Salmon stage III at diagnosis, receipt of 3 ormore lines of chemotherapy before AHCT, lack of chemosensitive disease prior to AHCT,AHCT ≥ 12 months from diagnosis and later year of AHCT.

Progression-free Survival and Overall SurvivalFigure 3 shows the probability of PFS. The 1 and 5 year probabilities of PFS were similar inboth groups. At 1 year it was 68% (95% CI 66–70%) in whites vs. 68% (95% CI 63–74%) inblacks. At 5 years it was 21% (95% CI 18–23%) vs. 19% (95% CI 14–25%) in whites andblacks respectively. In multivariate analysis (Table 4), race was not associated with PFS.

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Figure 4 shows the probability of overall survival after AHCT. The 1 and 5 year survival rateswere also similar between the two cohorts. At 1 year it was 87% (95% CI 85–88%) in whitesvs. 90% (95% CI 87–93%) in blacks. At 5 years it was 47% (95% CI 44–49%) vs. 52% (95%CI 45–59%) in whites and blacks respectively. In multivariate analysis (Table 4), race was nota significant predictor of survival.

PFS and overall survival were worse in patients with older age at AHCT (>50 years), KPSscore <90, higher Durie-Salmon stage, those who received two or more lines of therapy priorto AHCT, AHCT ≥ 12 months from diagnosis and chemotherapy resistant disease (Table 4).Overall survival was also lower in patients who underwent AHCT prior to 2002.

The major cause of mortality in both cohorts was relapse or progression of MM that accountedfor 72% of all deaths.

DiscussionOur analysis establishes that black and whites have very similar outcomes after AHCT forMM. These results concur with observations in other studies of non-transplant therapy that thedisparity in outcomes for MM disappears when blacks receive identical therapy.28

Several investigators have shown that blacks have outcomes similar to whites when given thesame non-transplant treatment for MM. Rohatgi et al showed that blacks were less likely toreceive chemotherapy but they responded with similar outcomes when given similar non-transplant therapy for MM.24 In the pre-transplant era, Modiano et al. retrospectively evaluatedthe impact of race in the results of the SWOG 8829 study of conventional chemotherapy forMM.25 From 99 study sites in the US, 116 black and 467 white patients were shown to havesimilar median survival (32 and 30 months, respectively). There were no differences by stageor MM subtype. A smaller study from the Department of Defense equal access health caresystem, reported on the outcomes of 36 black and 55 white newly diagnosed patients receivingAHCT for MM and observed comparable outcomes between the two groups.26 In their study,there were no differences in the stage, hemoglobin, calcium or creatinine levels, althoughblacks did have higher CRP levels and a trend for less skeletal involvement. The authorsrecommended a larger retrospective study such as the current one. Other single center analysescomparing black and white recipients of AHCT for MM have drawn conflicting conclusions.Khaled et al. analyzed 101 black patients and concluded that they were likely to relapse earlierafter AHCT.27 Survival was not compared in this study. Saraf et al. in their comparative studythat included 38 black and 32 white AHCT recipients, found that black patients had moreprolonged responses and greater event free survival.28

Unfortunately, there is ample evidence that blacks are less likely to receive chemotherapy forMM as well as AHCT. Rohatgi et al. reviewed patterns of chemotherapy use for patients withMM outside the clinical trial setting.24 From a population based retrospective cohort of 49,021patients of age 65 years or older with stage II or III MM, they found that only 52% receivedchemotherapy. Blacks were less likely to receive chemotherapy compared to whites (47.6%vs. 52.8%) despite evidence that use of chemotherapy decreased all cause mortality, myelomaspecific mortality and increased survival. 24 The reasons for the disparate access are unclear,since controlling for socioeconomic status did not eliminate the disparity in the receipt ofchemotherapy.

These disparities in the receipt of therapy occur in the transplant setting as well. Joshua et al,in a previous study from the CIBMTR demonstrate that whites are more likely to receive AHCTfor newly diagnosed MM compared to an age and sex adjusted black population.19 Using datafrom the SEER and CIBMTR registries, the study showed that age and sex adjusted odds ofreceiving AHCT for MM is 1.72 times greater in whites compared to blacks. Although our

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study cannot address the reasons for this under utilization of AHCT in blacks, interestingconclusions can be drawn regarding AHCT for MM in black patients.

It has been proposed that reduced access to treatment for myeloma may be related to actual orperceived worse outcomes in black patients. Our study clearly shows that outcomes are notdifferent between blacks and whites receiving AHCT for MM suggesting this treatmentmodality should be offered to all patients when medically appropriate. These results are inaccordance with a meta-analysis of patients treated for 14 different cancers, where survival inthe majority of cancers was similar between races when comparable treatment was given.29

The pre-transplant characteristics of black recipients of AHCT are interesting. The black cohortwas younger and had better performance status than the white cohort, despite higher rates ofanemia and other co- morbidities at diagnosis. These differences likely indicate a selection biasoperating against older black patients with lower KPS scores with regard to referral forconsideration of AHCT. Black patients were also likely to have had a longer time betweendiagnosis and transplantation compared to whites, while receiving a similar number ofchemotherapy regimens and having similar responses. This suggests delayed referral forconsideration of AHCT. A referral bias favoring only the healthiest black patients for transplantmay be in effect, while patients with less favorable clinical features may only be offered non-transplant or even non-treatment options.

The major strength of our study is the broad representation of transplant centers making it verylikely that these results are applicable to the transplant community as a whole. In this analysiswe are unable to draw any conclusions about factors associated with non-receipt of transplantin blacks since a non-transplant population is not represented. The characteristics of thepopulation of black MM patients not receiving AHCT need to be analyzed to identify the causesof a under utilization of AHCT. It is possible that many blacks who are not receiving stem-celltransplantation for myeloma are forgoing the transplant by choice. However it is also possiblethat referral bias, unequal access to tertiary care, compliance gap, reluctance to enter clinicaltrials and socioeconomic disparities account for some of the differences in utilization of AHCTfor patients with MM. With the demonstration of equal outcomes for black with MM, furtherstudy and definitive action to ensure better awareness and delivery of transplant options forthe black population is warranted.

AcknowledgmentsThe CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the NationalCancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergyand Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contractHHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two GrantsN00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna;American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical Collegeof Wisconsin; Association of Medical Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc.; BaxterInternational, Inc.; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and Blue ShieldAssociation; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corporation;CellGenix, GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and ConsultingServices; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an InvitrogenCompany; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gambro BCT, Inc.;Gamida Cell, Ltd.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.;Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; Merck & Company; The MedicalCollege of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.;Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; NaturePublishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.;Otsuka Pharmaceutical Development & Commercialization, Inc.; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc;Pharmion Corporation; Saladax Biomedical, Inc.; Schering Plough Corporation; Society for Healthcare Epidemiologyof America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex; Teva Pharmaceutical Industries; The MarrowFoundation; THERAKOS, Inc.; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories;ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position

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of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency ofthe U.S. Government.

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Figure 1.Cumulative incidence of non-relapse mortality

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Figure 2.Cumulative incidence of disease relapse and progression

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Figure 3.Probability of progression-free survival

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Figure 4.Probability of overall survival

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Table 1

Patient Characteristics

White Black

Variable N (%) N (%) P-valueb

Number of patientsa 1892 303

Age median (range), years 57 (27–80) 55 (27–74) <0.001

Age group at transplant, years 0.002

 <50 396 (21) 88 (29)

 50–64 1111 (59) 172 (57)

 ≥ 65 385 (20) 43 (14)

Male sex 1136 (60) 164 (54) 0.05

Karnofsky score pre-transplant 0.005

 ≥ 90 1153 (61) 210 (69)

Hypertension <0.001

 Yes 471 (25) 143 (47)

Diabetes <0.001

 Yes 169 (9) 50 (17)

Body Mass Index 0.01

 Underweight/Normal (<25) 557 (29) 67 (22)

 Overweight (25–29.9) 741 (39) 120 (40)

 Obese/Morbidly Obese (≥ 30) 594 (31) 116 (38)

Disease related

Durie-Salmon stage at diagnosis 0.25

 I 203 (11) 25 (8)

 II 562 (30) 101 (33)

 III 1127 (60) 177 (58)

Immunochemical subtype of myeloma 0.34

 IgG 1003 (53) 173 (57)

 IgA 359 (19) 45 (15)

 Light chain 329 (17) 54 (18)

 Others/Unknown 125 (11) 16 (10)

Albumin level at diagnosis 0.05

 > 3.5 g/dL 732 (39) 101 (33)

Hemoglobin at diagnosis <10 g/dL <0.001

 < 10 g/dL 552 (29) 135 (45)

Creatinine at diagnosis 0.09

 >1.5 mg/dL 361 (19) 74 (24)

B-2 microglobulin level at diagnosis 0.83

 ≥ 5.5 mg/L 195 (10) 31 (10)

Prior chemotherapy regimens 0.78

 MP ± others 334 (18) 50 (17)

 VAD ± others (not MP) 1104 (58) 182 (60)

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White Black

Variable N (%) N (%) P-valueb

 Cy ± others 300 (16) 52 (17)

 Corticosteroids ± others 154 (8) 19 (6)

Number of lines of chemotherapyd 0.29

 1 1125 (59) 167 (55)

 2 536 (28) 99 (33)

 >2 231 (12) 37 (12)

Sensitive to chemotherapy prior to transplant 0.83

 Sensitive 1434 (76) 228 (75)

Disease status at time of transplant 0.67

 Complete Remission/Partial Remission 1396 (74) 231 (76)

Treatment related

Time from diagnosis to transplant median (range),months

8 (<1–249) 9 (2–217) <0.001

Time from diagnosis to transplant <0.001

 <12 months 1364 (72) 190 (63)

 ≥ 12 months 528 (28) 113 (37)

Conditioning regimen 0.7

 Melphalan only 1417 (75) 223 (74)

 Melphalan + TBI ± others 204 (11) 35 (12)

 Bu-Cy ± others (not TBI, not melphalan) 271 (15) 45 (15)

Median follow-up of survivors, median (range) 61 (<1–145) 51 (<1–132)

Abbreviations: MP=Melphalan+Prednisone VAD = vincristine+dexamethasone+adriamycin; Cy = cyclophosphamide; Bu = busulfan; TBI = totalbody irradiation; Eval = evaluable.

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Table 2

Variables tested in multivariate analysis.

Main effect variable:

Race/ethnicity: White* vs. Black

Patient-related variables:

Age: < 50* vs. 50–64 vs. ≥ 65

Gender: Male* vs. Female

Karnofsky performance status at transplant: <90% vs. ≥ 90%* vs. missing

Body Mass Index: underweight/normal* vs. overweight vs. obese/morbidly obese

Hypertension anytime prior to transplant: Yes* vs. No

Diabetes anytime prior to transplant: Yes* vs. No

History of smoking prior to transplant: Yes* vs. No

Creatinine >1.5 mg/dL vs ≤ 1.5* mg/dL at diagnosis

MM subtype: IgG vs. IgA vs. Light chain vs. Others/Unknown

Disease-related variables:

Durie-Salmon stage at diagnosis: I* vs. II vs. III

Number of lines of chemotherapy: 0 vs. 1* vs. 2 vs. >2

Sensitivity to chemotherapy prior to transplant: sensitive* vs. Others

Disease status prior to transplant: complete remission/partial remission* vs. others (includes minimal response, noresponse, stable disease, relapse/progressive disease and unknown)

Prior chemotherapy regimens: MP* vs. VAD vs. Cy ± others vs. Corticosteroids ± others

Transplant-related variables:

Time from diagnosis to transplant: <12 months* vs. Others

Conditioning regimen: Melphalan only* vs. melphalan + TBI ± others vs. Bu-Cy ± others (not TBI, not melphalan)

Purging: yes* vs no

Year of transplant: 1995–2001 vs. 2002–2005*

Abbreviations: MP=Melphalan+Prednisone VAD = vincristine+dexamethasone+adriamycin; Cy = cyclophosphamide; Bu = busulfan; TBI = totalbody irradiation

*Reference group

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Tabl

e 3

Mul

tivar

iate

ana

lysi

s for

rela

pse

and

non-

rela

pse

mor

talit

y

Rel

apse

Non

-Rel

apse

mor

talit

y

Var

iabl

eN

RR

P-va

lue

NR

RP-

valu

e

Rac

e

 W

hite

1850

1.00

a18

501.

00a

 B

lack

296

0.92

(0.7

8–1.

08)

P =

0.28

296

1.16

(0.7

5–1.

80)

P =

0.51

Patie

nt A

ge

 <

5047

51.

00a

P <

0.00

1

 50

–64

1253

1.55

(1.0

1–2.

39)

P =

0.05

 ≥

6541

83.

50 (2

.17–

5.65

)P

< 0.

001

Kar

nofs

ky S

core

prio

r to

cond

ition

ing

 <9

081

51.

00a

815

1.00

a

 ≥

9013

310.

88 (0

.79–

0.98

)P

= 0.

0213

310.

72 (0

.53–

0.98

)P

= 0.

03

Dur

ie-S

alm

on st

age

at d

iagn

osis

 I

222

1.00

aP

< 0.

001

222

1.00

aP

= 0.

004

 II

652

1.23

(1.0

0–1.

51)

P =

0.05

652

0.61

(0.3

5–1.

06)

P =

0.08

 II

I12

721.

54 (1

.27–

1.87

)P

< 0.

001

1272

1.16

(0.7

1–1.

88)

P =

0.56

Num

ber o

f lin

es o

f che

mot

hera

pyc

 1

1256

1.00

aP

= 0.

001

 2

628

1.12

(0.9

9–1.

27)

P =

0.07

 >

226

21.

39 (1

.16–

1.66

)P

< 0.

001

Sens

itivi

ty to

che

mot

hera

py p

rior t

o tra

nspl

ant

 O

ther

522

1.00

a

 Se

nsiti

ve16

240.

76 (0

.67–

0.85

)P

< 0.

001

Tim

e fr

om d

iagn

osis

to tr

ansp

lant

 <

12 m

onth

s15

191.

00a

 ≥

12 m

onth

s62

71.

19 (1

.04–

1.35

)P

= 0.

009

Yea

r of t

rans

plan

t

 19

95–2

001

1331

1.00

a13

311.

00a

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Rel

apse

Non

-Rel

apse

mor

talit

y

Var

iabl

eN

RR

P-va

lue

NR

RP-

valu

e

 20

02–2

005

815

1.17

(1.0

4–1.

31)

P =

0.00

881

50.

56 (0

.39–

0.81

)P

= 0.

002

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Tabl

e 4

Mul

tivar

iate

ana

lysi

s for

ove

rall

surv

ival

and

pro

gres

sion

-fre

e su

rviv

al

Ove

rall

Surv

ival

Prog

ress

ion-

free

surv

ival

Var

iabl

eN

RR

P-va

lue

NR

RP-

valu

e

Rac

e

 W

hite

1892

1.00

a18

501.

00a

 B

lack

303

0.94

(0.7

8–1.

13)

P =

0.50

296

0.94

(0.8

1–1.

09)

P =

0.39

Patie

nt A

ge

 <

5048

41.

00a

Pb < 0

.000

147

51.

00a

P =

0.03

 50

–64

1283

1.26

(1.0

9–1.

46)

P =

0.00

212

531.

12 (0

.99–

1.27

)P

= 0.

08

 ≥

6542

81.

52 (1

.26–

1.83

)P

< 0.

0001

418

1.24

(1.0

6–1.

46)

P =

0.00

7

Kar

nofs

ky S

core

prio

r to

cond

ition

ing

 <9

083

21.

00a

815

1.00

a

 ≥

9013

630.

74 (0

.66–

0.83

)P

< 0.

0001

1331

0.87

(0.7

9–0.

97)

P =

0.00

9

Dur

ie-S

alm

on st

age

at d

iagn

osis

 I

228

1.00

aPb <

0.0

001

222

1.00

aP

< 0.

0001

 II

663

1.13

(0.8

9–1.

44)

P =

0.32

652

1.12

(0.9

3–1.

36)

P =

0.23

 II

I13

041.

67 (1

.34–

2.09

)P

< 0.

0001

1272

1.49

(1.2

5–1.

79)

P <

0.00

01

Num

ber o

f lin

es o

f che

mot

hera

pyc

 1

1292

1.00

aPb <

0.0

001

1256

1.00

aP

= 0.

0002

 2

635

1.10

(0.9

6–1.

27)

P =

0.17

628

1.13

(1.0

0–1.

27)

P =

0.04

 >

226

81.

66 (1

.37–

2.01

)P

< 0.

0001

262

1.41

(1.1

9–1.

67)

P <

0.00

01

Sens

itivi

ty to

che

mot

hera

py p

rior t

o tra

nspl

ant

 O

ther

533

1.00

a52

21.

00a

 Se

nsiti

ve16

620.

82 (0

.72–

0.94

)P

= 0.

003

1624

0.76

(0.6

8–0.

85)

P <

0.00

01

Tim

e fr

om d

iagn

osis

to tr

ansp

lant

 <

12 m

onth

s15

541.

00a

1519

1.00

a

 ≥

12 m

onth

s64

11.

16 (1

.01–

1.34

)P

= 0.

0462

71.

16 (1

.03–

1.31

)P

= 0.

01

Biol Blood Marrow Transplant. Author manuscript; available in PMC 2011 March 1.